840506-29-8

Basic information

• Product Name: Acelarin
• Synonyms: Acelarin;N-(2'-Deoxy-2',2'-difluoro-P-phenyl-5'-cytidylyl)-L-alanine phenylmethyl ester;NUC-1031;NUC-1031 impurity
• CAS NO: 840506-29-8
• Molecular Formula: C₂₅H₂₇F₂N₄O₈P
• Molecular Weight: 580.4744474
• EINECS: -0
• Mol File: 840506-29-8.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 708.4±70.0 °C(Predicted)
• Appearance: /
• Density: 1.51±0.1 g/cm3(Predicted)
• PKA: 11.46±0.70(Predicted)
• CAS DataBase Reference: Acelarin(CAS DataBase Reference)
• NIST Chemistry Reference: Acelarin(840506-29-8)
• EPA Substance Registry System: Acelarin(840506-29-8)

Safety Data

• Hazardous Substances Data: 840506-29-8(Hazardous Substances Data)

Usage

Description

Acelarin, also known as the first anti-cancer ProTide to enter the clinic, is a phosphoramidate transformation of the pancreatic and ovarian cancer chemotherapy Gemcitabine. It is designed to improve the delivery and efficacy of Gemcitabine, making it a promising pharmaceutical candidate for cancer treatment.

Uses

Used in Oncology:
Acelarin is used as a chemotherapy agent for the treatment of pancreatic and ovarian cancers. It is a ProTide form of Gemcitabine, which allows for improved delivery and bioavailability, leading to enhanced therapeutic outcomes.
Used in Pharmaceutical Industry:
Acelarin is used as a novel drug candidate in the pharmaceutical industry for the development of new cancer treatments. Its unique ProTide structure offers advantages over traditional chemotherapy agents, making it a valuable asset in the fight against cancer.

Upstream product

• 183370-70-9 phenyl(benzyloxy-L-alaninyl)phosphorochloridate 
• 250698-51-2 (2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4,4-difluoro-2-(hydroxymethyl)tetrahydrofuran-3-yl tert-butyl carbonate 
• 5557-81-3 L-alanine benzyl ester hydrochloride 
• 122111-03-9 gemcitabine hydrochloride 
• 770-12-7 O-phenyl phosphorodichloridate 
• 95058-81-4 gemcitabine 

Downstream Products

• 1562406-27-2 benzyl ((S)-(((2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4,4-difluoro-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate 
• 1562406-27-2 2’-deoxy-2’,2’-difluoro-D-cytidine-5’-O-[phenyl(benzyloxy-L-alaninyl)]-(R)-phosphate 

Relevant articles and documents

Influence of 4′-Substitution on the Activity of Gemcitabine and Its ProTide against VZV and SARS-CoV-2

In addition to its therapeutic value as a chemotherapy drug, gemcitabine is of ongoing interest to the scientific community for its broad-spectrum antiviral activity. Herein the synthesis of 4′-methoxy- and 4′-fluoro-substituted gemcitabine analogues along with their phosphoramidate prodrugs is described. Among these derivatives, 4′-fluorogemcitabine proved to be active against varicella zoster virus (VZV, TK+ strain) with an EC50 of 0.042 μM and produced significant cytotoxicity (CC50 = 0.11 μM). Upon derivatization of this trifluoro nucleoside as its prodrug, decreased anti-VZV activity was observed, but with a concomitantly improved selectivity index (SI = 36). When this prodrug was tested against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its antiviral activity (EC50 = 0.73 μM) was comparable to or slightly lower than its cytotoxic concentration in measurements of cell growth and cell morphology, respectively.

Composition Rich in Single Isomer NUC-1031 and Preparation Method and use Thereof

Provided is a preparation method of a composition enriched in compound Sp-1. The method performs isomer separation on a reaction product from the first step, and then performs a two-step chemical synthesis, so as to prepare a composition comprising high-purity compound Sp-1, wherein the HPLC purity of the single isomer Sp-1 is 90% or more. Provided is a composition enriched in compound Sp-1. The composition has an inhibitory effect on tumor cell proliferation in vitro significantly higher than that of NUC-1031 and compound Rp-1. Also provided are the use of the composition, and a pharmaceutical composition comprising the composition and at least one pharmaceutically acceptable excipient.

Application of ProTide technology to gemcitabine: A successful approach to overcome the key cancer resistance mechanisms leads to a new agent (NUC-1031) in clinical development

Gemcitabine is a nucleoside analogue commonly used in cancer therapy but with limited efficacy due to a high susceptibility to cancer cell resistance. The addition of a phosphoramidate motif to the gemcitabine can protect it against many of the key cancer resistance mechanisms. We have synthesized a series of gemcitabine phosphoramidate prodrugs and screened for cytostatic activity in a range of different tumor cell lines. Among the synthesized compounds, one in particular (NUC-1031, 6f) was shown to be potent in vitro. Importantly, compared with gemcitabine, 6f activation was significantly less dependent on deoxycytidine kinase and on nucleoside transporters, and it was resistant to cytidine deaminase-mediated degradation. Moreover, 6f showed a significant reduction in tumor volumes in vivo in pancreatic cancer xenografts. The ProTide 6f is now in clinical development with encouraging efficacy signals in a Phase I/II study, which strongly supports the ProTide approach to generate promising new anticancer agents.